Gilead buys what it tried with Tubulis

Not long after spending $7.8bn on Arcellx Gilead is splashing $3.15bn on the antibody-drug conjugate developer Tubulis. While the former deal came in the crowded BCMA arena, there’s much less competition for Tubulis’s lead project, the NaPi2b-targeting TUB-040.

However, the transactions do have something in common, with Gilead both times opting for a “try before you buy” approach. The big biotech had partnered with Arcellx since 2022, and with privately held Tubulis since December 2024.

Still, the previous agreement with Tubulis, worth $20m up front, only concerned an option over an ADC against an undisclosed solid tumour target. Now Gilead has gone all in, after gaining “strong conviction in [Tubulis’s] programmes and research capabilities”, it said on Tuesday.

Napistar

As a target NaPi2b had looked like a dead end after Mersana scrapped not one but two clinical-stage assets, and Roche and Zymeworks also dropped out of the running.

However, Tubulis revived hopes at last year’s ESMO meeting, when the phase 1/2 Napistar1-01 trial showed a 50% confirmed response rate among 46 platinum-resistant ovarian cancer patients given 1.67-3.3mg/kg doses of TUB-040.

At the time, Munich-based Tubulis said it planned to “rapidly advance” the project into pivotal trials, as well as looking at earlier-stage disease and other tumour types. Napistar1-01 is also evaluating the asset in adenocarcinoma NSCLC.

TUB-040 uses a topoisomerase 1 inhibitor payload, while the discontinued assets from Mersana (upifitamab rilsodotin and XMT-1592) and Roche (lifastuzumab vedotin) employed tubulin inhibitor payloads. Zymeworks’ ZW220, meanwhile, used a topo1 payload, but the decision to pause that project looked like a question of priorities.

Tubulis also has a unique selling point in its phosphorus-based conjugation chemistry, which it calls P5, and which it says can help avoid premature release of the payload, thereby increasing payload in the tumour and sparing healthy tissues.

Competition for TUB-040 could come from MediLink’s YL205, a topo1-based ADC that uses that company’s Tmalin “activable” linker-payload technology, in a global phase 1/2 solid tumour trial; and Sino’s (LaNova’s) NaPi2b x 4-1BB bispecific antibody LM-2417, which went into a Chinese phase 1/2 last September. So far, though, 4-1BB co-stimulation has disappointed.

There are various NaPi2b-targeting preclinical projects, notably a dual payload ADC from Araris, ARC-201.

Pipeline

The latest deal, which carries milestones of up to $1.85bn, will also give Gilead a pipeline of other ADCs. This includes TUB-030, which hits 5T4 and is in a phase 1/2 solid tumour study.

There’s more activity against this target, but other ADCs are also early. Notably, at ESMO Salubris claimed a 38% ORR among 13 NSCLC patients receiving its biparatopic contender JK06 during dose escalation; however, there was one death from pneumonitis at the higher doses tested.

The targets for Tubulis’s other pipeline assets remain undisclosed, although the group has said it’s working on degrader antibody conjugates and novel payloads. It also has an alliance with Bristol Myers Squibb over next-generation ADCs, signed in 2023. Last year Tubulis noted that the first project from this deal had entered the clinic, but didn’t give further details.

Tubulis, which banked a €308m series C financing round last October, will operate as a “dedicated ADC research organisation” within Gilead. The bigger group already has an approved TROP2-targeting ADC, Trodelvy, gained via its much maligned $21bn purchase of Immunomedics.

Tubulis’s pipeline

Source: OncologyPipeline & company website.